This Project is a joint effort of four investigators to study how tissue- specific expression of oncogene products relates to oncogenesis. Much of the effort can be categorized under three questions: What are the functions of oncogenes? How can oncogene expression be controlled to give tissue-specific activation in animals? What are the consequences of the tissue-specific expression of different oncogenes? The oncogenes that will be of primary interest will be ab1, myc, and ras. The role of myc in preventing differentiation will be an important theme. The role the tyrosine-specific kinase encoded by ab1 will be studied using both genetics and biochemical methods. Recombinant DNA methods will be used to develop retrovirus-based vectors for integrating oncogenes into embryonic cells of the mouse fetus. By inserting appropriate control regions into the vectors, tissue-specific expression of the oncogenes will be attempted to allow the oncogenic spectrum of each oncogene to be ascertained. A prominent system for obtaining tissue-specific transcriptional signals will be the immunoglobulin genes. Vectors will be integrated into both pre-implantation and post- implantation mouse embryos to study their properties in both early and later fetal cells.